Means of promoting nitrogen conservation under conditions of low nitrogen intake will be examined with an aim to reducing waste nitrogen accumulation and improving nutrition in subjects with impaired mechanisms of nitrogen disposal as well as in normal subjects on restricted nitrogen intake. Urea formation in such subjects will be studied as a function of plasma levels of amino acids and ammonium, and related metabolic intermediates. The ability of nitrogen-free analogues of essential amino acids to reduce nitrogen wastage will be studied to determine if it occurs solely by modifying the relative concentrations of these substances or by other mechanisms as well. The protein-sparing effects of branched-chain ketoacids, in particular, will be explored to determine whether it is attributable to an effect on protein synthesis or degradation. The efficacy of these three analogues in portal-systemic encephalopathy will be studied. The long-term efficacy of nitrogen-free analogues in children and adults with chronic renal failure will be examined. The utility of analogues in patients with congenital hyperammonemia will be studied with the aid of experimental models of urea cycle defects. In addition, new means for detecting these disorders prenatally, for screening neonates, and for detecting heterozygotes will be explored, and tracer studies of ureagenesis carried out. Newer analogues to be examined, chiefly in renal failure, include hydroxy-analogues of tyrosine, methionine and histidine as well as stereoisomers of the keto-analogues of isoleucine.